Nature relies on proven strategies
Publication in Nature Genetics: Newly discovered mechanism could suppress development of polycystic kidney disease
Prof. Gerd Walz, Jun. Prof. Dr. Olaf Ronneberger | Freiburg researchers from the Department of Nephrology at the Freiburg University Medical Center under Prof. Dr. Gerd Walz, member of BIOSS Centre for Biological Signalling Studies, and Olaf Ronneberger, junior professor at BIOSS, have made an important contribution to the elucidation of kidney development. With the help of high-resolution microscopy, Dr. Soeren Lienkamp succeeded in tracing and explaining early organ development in miniscule frog kidneys: In this phase, globular objects must develop into elongated kidney tubes that are vitally important for kidney function later on. |
Effective Elongation of the Tissue
The scientists discovered that the individual cells gather together to form a so-called rosette, a circular arrangement in which they are all touching each other at a single point, in the maturing frog kidney. This rosette stretches the tissue by turning in the direction of the later kidney tube. This is a principle also used by fruit flies in order to produce fully functional, elongated wings out of tiny clumps of tissue. Nature evidently uses components that have proven to be effective once in the course of evolution again and again with only slight modifications. In addition, the research group led by Gerd Walz, medical director of the Department of Nephrology at the Freiburg University Medical Center, demonstrated in cooperation with groups in Freiburg und Texas that this program also plays a role in mouse development and thus probably also in that of humans. “Not only were we able to show how clever nature is at following up on discoveries it has once made, we also emphasized once again how much we can still learn today from fruit flies and tadpoles about the development of organs and disease processes,” explains the BIOSS member.
Formation of Cysts Could be Prevented from the Outset
Indeed, the findings have direct applications for the treatment of polycystic kidney disease, which researchers at the Department of Nephrology in Freiburg have already been studying for many years. “Up to now we have been trying to find ways to suppress the growth of cysts in patients who have inherited this disease. Now we can prevent the formation of cysts from the outset by increasing the activity of elongation programs like those we have described. This means that we have a completely new approach for preventing the disease in the early stages of development.” Now all the scientists need to do is find drugs that can stimulate these programs. “Nature itself shows that this must be possible,” says Gerd Walz. “There are genetic defects in mice that lead to polycystic kidney disease in humans. However, in the mouse the formation of cysts is arrested completely by an increased elongation. If that is possible with mice, there must also be possibilities for applying this principle to prevent cysts in humans.”
Originalpublikation
Vertebrate kidney tubules elongate using a planar cell polaritydependent, rosette-based mechanism of convergent extension.
Soeren S Lienkamp, Kun Liu, Courtney M Karner, Thomas J Carroll, Olaf Ronneberger, John B Wallingford & Gerd Walz.
Nat Genet. 2012 Nov 11. doi: 10.1038/ng.2452. [Epub ahead of print]
http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2452.html